When bacteria infect an organism, there’s a flurry of activity. Bacteria rush to take over their new host, unleashing their genetic weaponry inside the organism’s cells, while the host launches a defense to kill the invaders before too much harm is done. Feng Shao wants to understand the tactics behind every skirmish in this battle. To do so, he’s bridging the worlds of biology and chemistry in a multidisciplinary approach he hopes will explain the molecular arsenals both sides use in this long-fought war.
As an undergraduate in China, Shao studied chemistry. But when it came time to choose what to do next, he saw biology as a more exciting and quickly moving field. Many questions in chemistry had been answered, he recalls, but in biology, new questions arose almost daily. “I knew barely any biology,” he says. “I had no training in genetics, cell biology, developmental biology, or immunology. But biology, at the bottom line, is all determined by chemical reactions. And those I knew.”
Shao took a leap of faith and joined a graduate program in biophysics—a field that integrates chemistry, physics, and biology. It allowed him to apply his knowledge in chemistry to the study of immunology and other interesting topics in biology. When he finished his master’s degree at the Institute of Biophysics in Beijing three years later, his fascination with the field had grown stronger. The obvious next step was to pursue a Ph.D. in biology, which he did at the University of Michigan.
In Ann Arbor, Shao joined the lab of Jack E. Dixon, a professor and chair of biological chemistry at Michigan (now vice president and chief scientific officer at HHMI). With Dixon, Shao studied how multiple strains of the bacterium Yersinia—including the strain that causes the plague—infect cells by injecting six types of molecules called effectors into host cells. He identified a family of effectors produced by Yersinia that are also found in bacteria that infect plants—one of the first effectors known to exist in both animal and plant pathogens. Shao went on to discover how the effector causes the cytoskeleton of a cell to dysfunction.
At the same time Shao was working on his Ph.D., his wife, Xin Bian, was working in Ann Arbor and pursuing a master’s degree in business administration. His studies complete, he served as a postdoctoral fellow at the University of California, San Diego, and Harvard Medical School. Once Bian finished her M.B.A., the couple returned to Beijing, where Shao joined the faculty at the newly created National Institute of Biological Sciences. There, he continued his studies of effectors, a term encompassing the molecules that pathogens use to invade cells. In 2007, Shao and his team revealed how OspF, an effector from the bacterium Shigella flexneri, which causes dysentery, changes the signaling pathways in host cells. Understanding how effectors change pathways can help scientists develop ways to thwart the pathogen’s attack plan. In another study, Shao’s team looked at effectors from Legionella pneumophila, the bacterium that causes Legionnaires’ disease, and discovered an effector that mimics the way a cell turns on inflammatory pathways.
“I don’t focus on a particular pathogen like many in this field do,” Shao says. “I work with several different pathogens that have different life cycles. But they all have to face the same host immune system.”
The immune systems of mice and humans can recognize many invading cell types, Shao says, but how they do that was a mystery. Immune systems can’t identify all the potential effectors a pathogen might release as it attempts to infect a cell. But, Shao discovered, they do recognize the injection system that bacteria use to get the effectors into host cells.
“The injection system is more closely related between all these pathogens than the effectors are,” Shao explains. In 2011, he and his colleagues published a paper outlining how a family of proteins called NAIPs recognizes the components of bacterial injection systems and activates inflammasomes—immune system structures that prime the cells to fight off infection.
While Shao has immersed himself in the world of immunology and biology, he still calls on his chemistry background to do his research, using his multidisciplinary experience to study both sides of the pathogen–host interaction. Shao hopes to reveal how vital pathways in human cells work and how new antibiotics, for example, could fight infections.
“The process of discovery is so exciting to me,” Shao says. “The complexity of biology constantly exceeds my expectations.”